Hepatitis C virus (HCV) infection is the most important cause of chronic liver disease, cirrhosis, and liver cancer in the world with 4 million people having chronic HCV infections in the U.S. However, relatively little is known about its long-term natural history in the pediatric population. In Egypt the 18 percent population-based HCV prevalence is 10-fold greater than in the USA and our community-based data report 1-in-6 HCV infections are in children. Due to insufficient numbers of HCV infected pediatric cases at most sites, almost all reported studies have been conducted on heterogenous populations in multi-centered studies. Both the high prevalence of HCV and the high proportion of pediatric cases make Egypt ideal for conducting pediatric studies of HCV natural history. Objective: To develop a specialty clinic to provide care for, and prospectively follow an HCV-infected pediatric cohort in order to study the natural history of HCV in Egyptian children. We plan to enroll and follow-up children referred from the outpatient clinic attendees at Cairo University Children's Hospital (CUCH) and elsewhere. Our specific aims are: to gather preliminary data to describe the risk factors and liver function morbidity of HCV infection in children attending a specialized HCV clinic in the largest metropolitan referral pediatric hospital in Egypt. This project will provide a cohort of children for long-term observations of natural history of HCV infections. Methods: Over three years, we will screen 2000-to-3000 children referred to the HCV outpatient clinic in CUCH for HCV antibody (anti-HCV) testing using 3rd generation enzyme immunoassay (EIA) tests, and we will identify chronically infected children by testing for the presence of HCV RNA using reverse transcriptase polymerase chain reaction (RT-PCR). We will compare children who test positive for anti-HCV with anti-HCV negative age and gender-matched controls for risk factors and symptoms of chronic disease, and we will test their mothers for anti-HCV and HCV RNA and interview them for possible risk factors. We will assess liver function and morbidity in HCV infected children and their controls with clinical examinations, liver function tests, and abdominal ultrasound. This study will facilitate the enrollment of a rare cohort of HCV infected children that will be followed prospectively to further study the natural history of HCV, as well as possible future studies involving potential vaccines and treatment trials.